Staphylococcus aureus is one of the most important causes of life-threatening bacterial infections in the world. Recent isolation of S. aureus strains resistant to our most powerful antibiotics highlights the importance of identifying novel therapeutic targets. It has been shown previously that S. aureus can grow on heme and hemoglobin as a sole iron source, a process vital to staphylococcal pathogenesis. How S. aureus binds hemoproteins and metabolizes heme is not entirely clear. IsdH is a cell wall-anchored surface protein that has significant amino acid similarity to IsdB, a S. aureus hemoglobin receptor. One goal of this proposal is to characterize the hemoglobin receptor properties of IsdH and determine its role in pathogenesis. A second goal is to characterize a newly identified heme-regulated ABC-type transporter and evaluate its role in heme metabolism and pathogenesis. This ABC-type transporter and the surface protein IsdH are poorly understood components of S. aureus. Further characterization of the staphylococcal pathways for hemoprotein binding and heme metabolism may pave the way for the development of novel antimicrobials aimed at targeting these processes. [unreadable] [unreadable] [unreadable] [unreadable]